During routine research carried out by the Veterinary Laboratories Agency (VLA), test results have revealed a single case of H-type Bovine Spongiform Encephalopathy (BSE) in the UK in 2005. This form of BSE has already been identified in several other European countries in addition to Japan, Canada and the United States of America.

The cow died on a farm in Dumfries and Galloway at 13 years of age. The carcass was sampled and tested for BSE in accordance with EU requirements for testing all fallen stock aged over 24 months. Test results confirmed the presence of BSE. The carcass was incinerated and the offspring from this cow were culled in line with current BSE regulations.

In August 2006 the VLA began a retrospective examination of brain samples taken from previous BSE cases as part of a research programme designed to analyse different types of BSE in the national herd. The aim of the study is to determine whether unusual cases of BSE, had in fact occurred in the UK in the past. The studies are ongoing however this case has been identified as H-type. All forms of BSE are treated identically therefore no additional action would have been required in this case.

The Spongiform Encephalopathy Advisory Committee (SEAC) will examine all the available data on this case during a discussion of different forms of BSE worldwide at their next meeting on 10 th May 2007.

Notes to editors1) SEAC briefly discussed information on the different forms of BSE worldwide, at their February 2007 meeting. The background papers for that meeting are available at http://www.seac.gov.uk/agenda/agen200207.htm

2) Japan, the USA, Canada and several European countries (including France, the Netherlands, Sweden, Switzerland, and Germany) have reported H-type BSE. Japan and several European countries (including Italy, Denmark, Poland, Belgium and Germany) have reported L-type BSE. Both types have been reported predominantly in cattle over 10 years old. In both types, the abnormal prion protein (PrP Sc ) in these animals has different biochemical characteristics to that seen in BSE. Mice experimentally infected with the brains of these animals develop a disease which differs from that seen in BSE infected mice. In two L-type cases where the intact whole brain was studied, the pattern of deposition of PrP Sc in the brain differed from that in BSE.

http://www.defra.gov.uk/news/2007/070309b.htm

QUESTIONs FIRST PLEASE, maybe someone can answer this for me.

DOES H-type BSE found now in the U.K., and other EU countries, Japan, Canada and the USA, does this pathology look like sporadic CJD also, like the L-type BSE found in Japan and several European countries (including Italy, Denmark, Poland, Belgium and Germany), as opposed to the nvCJD pathology being like that of typical BSE ???

IN other words, does both H-type and L-type BSE differ from the BSE in relations to the nvCJD pathology in humans, and does both H-type and L-type BSE pathology look like some sporadic CJD phenotypes ???

HERE we report a bovine BSE case associated with a novel prion protein gene (Prnp) polymorphism resulting in an amino acid substitution. The animal carrying this mutation was positive for the abnormal prion protein, PrPBSE, in brainstem tissue. Western blot characterization of the PrPBSE of this animal revealed a high molecular weight phenotype of BSE when compared to PrPBSE from typical BSE isolates. AN IDENTICAL MUTATION IN THE HUMAN PRION PROTEIN SEQUENCE HOMOLOGUE HAS BEEN PREVIOUSLY DESCRIBED AS THE MOST COMMON CAUSE OF THE GENETIC HUMAN PRION DISEASES (gCJD, FFI and GSS). ...page 8...end

confusious is a bit confused here.....

thank you, kind regards,terry

CONSIDERATION OF FUTURE DISCUSSION OF UNUSUAL CASES OF SPONGIFORM ENCEPHALOPATHY IN CATTLE

molecular similarities have been described between two case of BASE found in Italy and a subtype of sporadic CJD...

snip...

Our observations underline the high susceptibility of a primate species to the BASE prion strain and provide a biochemical basis for the identification of a potential occurence in man. ...page 9...end

14. STUDIES ON THE SECOND ATYIPCAL BSE CASE IN A JAPANESE BLACK COW

snip...

SUCH a glycosylation-ratio is distinct from that of the typical BSE agent in which the di-glycosylated form is dominant (approx. 70%) but, INTRIGUINGLY, SIMILAR TO THAT OF THE TYPE-2 SPORADIC CJD AGENT.

snip...

JUDGING from the glycosylation-ration, BSE prion herein is different from the typical BSE prion, and the atypical BSE prion found previously in a Holstein steer in Japan. INSTEAD, its molecular feature is close, IF NOT IDENTICAL, to PrPSc found in the cattle succumbed to bovine amyloidtic spongiform encephalopathy, and to the sporadic CJD-like PrPSc in the mice inoculated with BSE agent. ...page 12...end

http://www.seac.gov.uk/papers/96-2.pdf

Research Project: Study of Atypical Bse Location: Virus and Prion Diseases of Livestock

2006 Annual Report

4d.Progress report. This report serves to document research conducted under a specific cooperative agreement between ARS and the Italian Reference Centre for Animal TSE (CEA) at the Istituto Zooprofilattico Sperimentale, Turin, Italy. Additional details of research can be found in the report for the parent project 3625-32000-073-00D, Transmission, Differentiation, and Pathobiology of Transmissible Spongiform Encephalopathies (TSEs).

The aim of the cooperative research project is (i) to compare the U.S. Bovine Spongiform Encephalopathy (BSE) isolates and the atypical BSE isolates identified in Italy and (ii) to determine whether diagnostic methods routinely used at the USDA are able to identify atypical BSE cases.

Within FY06, formalin fixed and frozen brain materials from animals with typical and atypical Italian (BASE) BSE have been sent by CEA to the USDA-ARS-NADC laboratory in Ames, IA. The serial brain material sections of BSE and BASE (consecutively numbered) will be analyzed in Ames using the USDA immunohistochemistry (IHC) protocol. To evaluate its reproducibility in Italian laboratories and to standardize the method, the USDA IHC protocol is being established at the CEA neuropathology laboratory. As soon as the Ventana NexES IHC Staining System is available to the CEA, the same samples (different cut numbers) will be examined by the CEA using the CEA in-house and the USDA IHC protocol.

In order to evaluate the USDA Western blot method, about 2 gram of typical Italian BSE and about 2 gram of atypical BASE brain tissue have been sent to the USDA-ARS-NADC laboratory. These samples and U.S. typical and atypical BSE samples have been analyzed in parallel using both the USDA and CEA Western blot methods and three different monoclonal antibodies (6H4, P4, SAF 84). These studies were performed during the visit by a CEA collaborator to the USDA-ARS-NADC. The latter studies revealed that both the Italian and USDA extraction and Western blot methods allowed the identification of the typical and atypical BSE samples tested.

Objective: The objective of this cooperative research project with Dr. Maria Caramelli from the Italian BSE Reference Laboratory in Turin, Italy, is to conduct comparative studies with the U.S. bovine spongiform encephalopathy (BSE) isolate and the atypical BSE isolates identified in Italy. The studies will cover the following areas: 1. Evaluation of present diagnostics tools used in the U.S. for the detection of atypical BSE cases. 2. Molecular comparison of the U.S. BSE isolate and other typical BSE isolates with atypical BSE cases. 3. Studies on transmissibility and tissue distribution of atypical BSE isolates in cattle and other species.

Approach: This project will be done as a Specific Cooperative Agreement with the Italian BSE Reference Laboratory, Istituto Zooprofilattico Sperimentale del Piemonte, in Turin, Italy. It is essential for the U.S. BSE surveillance program to analyze the effectiveness of the U.S diagnostic tools for detection of atypical cases of BSE. Molecular comparisons of the U.S. BSE isolate with atypical BSE isolates will provide further characterization of the U.S. BSE isolate. Transmission studies are already underway using brain homogenates from atypical BSE cases into mice, cattle and sheep. It will be critical to see whether the atypical BSE isolates behave similarly to typical BSE isolates in terms of transmissibility and disease pathogenesis. If transmission occurs, tissue distribution comparisons will be made between cattle infected with the atypical BSE isolate and the U.S. BSE isolate. Differences in tissue distribution could require new regulations regarding specific risk material (SRM) removal.

http://www.ars.usda.gov/research/projects/projects.htm?ACCN_NO=408490

2005 Annual Report

4d.Progress report. This report serves to document research conducted under a specific cooperative agreement between ARS and the Italian Reference Centre for Animal TSE (CEA) at the Istituto Zooprofilattico Sperimentale, Turin, Italy. Additional details of research can be found in then report for the parent project 3625-32000-073-00D, Transmission, Differentiation, and Pathobiology of Transmissible Spongiform Encephalopathies. The aim of the cooperative research project conducted by the CEA and ARS is to compare the U.S. bovine spongiform encephalopathy (BSE) isolate and the bovine amyloidotic spongiform encephalopathy isolates (BASE) identified in Italy. The first objective was to determine whether diagnostic methods routinely used by USDA are able to identify the Italian BASE cases. For this purpose, CEA received the immunohistochemistry (IHC) protocol developed by APHIS-USDA. The IHC protocol was reproduced and standardized in the CEA laboratory and will be applied to the Italian BSE and BASE cases. Furthermore, fixed brainstem sections and frozen brainstem material from Italian BSE and BASE cases will be sent to ARS for analysis using USDA IHC and Western blot (WB) methods. These studies will enable us to determine whether the present diagnostic tools (IHC and WB) employed at the USDA will be able to detect the Italian BASE cases and also enable us to compare Italian BSE and BASE with the U.S. BSE cases.

NEW findings of BASE in cattle in Italy of Identification of asecond bovine amyloidotic spongiform encephalopathy: Molecularsimilarities with sporadic

Creutzfeldt-Jakob disease

http://www.pnas.org/cgi/content/abstract/0305777101v1

Atypical BSEBecause of its contemporary nature, the study of atypical BSE is very much a work in progress, with comparatively little published data and many unknowns. The first 2 cases to be identified were a serendipitous discovery made in the course of an unrelated experimental study that required a detailed neuropathologic and immunochemical examination of the entire brain (5). The absence of clinical signs in these older animals, the unusual distribution of PrPTSE, together with amyloid plaques, and a Western blot pattern that differed from the stereotypic pattern seen in typical BSE left little doubt about the probability that a new "atypical strain" had been identified (bovine amyloidotic spongiform encephalopathy[BASE]).

Although no further cases were found in over 100 cattle examined in Italy, the initiation of Western blot studies of animals in other countries with screening test programs began to yield additional atypical patterns (Table 2, Figure 3) (6–14; P. Lind, pers. comm.). Two major patterns have been described, named L (resembling the original Italian case pattern with a lower molecular weight than typical BSE) and H (for a distinct pattern first seen in France with a higher molecular weight than typical BSE). It is not yet clear whether other mixed patterns result from technical procedures in different laboratories or whether a more complicated scheme of classification will evolve as more atypical patterns are discovered.

In addition, Western blots of PrPTSE are a fragile basis on which to define a BSE phenotype. Little or no information is available about either the clinical status or neuropathologic features of these animals. We know that cases have occurred in different breeds and PrP genotypes, and we also know that very few of the animals have had the typical clinical picture of BSE (behavioral disturbances, sensory signs, ataxia, and tremors), but a cloud of ambiguity surrounds the clinical picture even in those animals for which an extensive post-hoc investigation was undertaken. The fact that few detailed neuropathologic results are available is explained by the need to preserve at least a full half brain for examination, which is presently not done in any of the various countries that have screening test programs. In the future, the brain as well as the carcass must be retained in cold storage until the test results are known.

The frequency of atypical cases is another unknown. Published (7,12) and unpublished (11,13) observations indicate that in some countries it might be as high as 5%–10% of the total number of older animals diagnosed by rapid screening tests (e.g., 2/27 in Germany, and 1/9 in Canada), which would seem to be a surprisingly high proportion of spontaneously occurring cases. However, data are not yet sufficient to estimate the overall prevalence of atypical BSE, i.e., cases per million tested animals of all ages.

In this context, a word is in order about the US testing program. After the discovery of the first (imported) cow in 2003, the magnitude of testing was much increased, reaching a level of >400,000 tests in 2005 (Figure 4). Neither of the 2 more recently indigenously infected older animals with nonspecific clinical features would have been detected without such testing, and neither would have been identified as atypical without confirmatory Western blots. Despite these facts, surveillance has now been decimated to 40,000 annual tests (USDA news release no. 0255.06, July 20, 2006) and invites the accusation that the United States will never know the true status of its involvement with BSE.

In short, a great deal of further work will need to be done before the phenotypic features and prevalence of atypical BSE are understood. More than a single strain may have been present from the beginning of the epidemic, but this possibility has been overlooked by virtue of the absence of widespread Western blot confirmatory testing of positive screening test results; or these new phenotypes may be found, at least in part, to result from infections at an older age by a typical BSE agent, rather than neonatal infections with new "strains" of BSE. Neither alternative has yet been investigated.

UPI previously reported that from 2001 to 2003 the USDA collected the wrong part of the brain in more than 200 cows that were being screened as part of its BSE surveillance program.

The USDA documents also indicate the agency never was able to identify or test 52 cows that came into the United States in 2001 along with the Washington cow that tested positive in 2003. Of these, 11 were considered to be "high risk" because they were born within a year and on the same premises as the infected cow.

These cows may have gone into the food supply and been consumed by people. The concern is humans can contract a fatal brain disease from eating beef products contaminated with the mad cow pathogen.

THE USDA JUNE 2004 ENHANCED BSE SURVEILLANCE PROGRAM WAS TERRIBLY FLAWED ;

CDC DR. PAUL BROWN TSE EXPERT COMMENTS 2006

The U.S. Department of Agriculture was quick to assure the public earlierthis week that the third case of mad cow disease did not pose a risk tothem, but what federal officials have not acknowledged is that this latestcase indicates the deadly disease has been circulating in U.S. herds for atleast a decade.

The second case, which was detected last year in a Texas cow and which USDAofficials were reluctant to verify, was approximately 12 years old.

These two cases (the latest was detected in an Alabama cow) present apicture of the disease having been here for 10 years or so, since it isthought that cows usually contract the disease from contaminated feed theyconsume as calves. The concern is that humans can contract a fatal,incurable, brain-wasting illness from consuming beef products contaminatedwith the mad cow pathogen.

"The fact the Texas cow showed up fairly clearly implied the existence ofother undetected cases," Dr. Paul Brown, former medical director of theNational Institutes of Health's Laboratory for Central Nervous SystemStudies and an expert on mad cow-like diseases, told United PressInternational. "The question was, 'How many?' and we still can't answerthat."

Brown, who is preparing a scientific paper based on the latest two mad cowcases to estimate the maximum number of infected cows that occurred in theUnited States, said he has "absolutely no confidence in USDA tests beforeone year ago" because of the agency's reluctance to retest the Texas cowthat initially tested positive.

USDA officials finally retested the cow and confirmed it was infected sevenmonths later, but only at the insistence of the agency's inspector general.

"Everything they did on the Texas cow makes everything USDA did before 2005suspect," Brown said. ...snip...end

"Actually, Terry, I have been critical of the USDA handling of the mad cow issue for some years, and with Linda Detwiler and others sent lengthy detailed critiques and recommendations to both the USDA and the Canadian Food Agency."

TEXAS ATYPICAL BSE IN BOVINE FINALLY CONFIRMED ALMOST ONE YEAR AFTER FACT BY OIG DOING END AROUND JOHANNS ET AL, or that cow would have never been confirmed. 48 HOUR turnaround for confirmation of suspect BSE case by BSE guidelines flaunted until OIG finally stepped in. ...tss

WASHINGTON, June 24, 2005 -- Agriculture Secretary Mike Johanns today announced that the U.S. Department of Agriculture has received final test results from The Veterinary Laboratories Agency in Weybridge, England, confirming that a sample from an animal that was blocked from the food supply in November 2004 has tested positive for bovine spongiform encephalopathy (BSE). Johanns also directed USDA scientists to work with international experts to thoughtfully develop a new protocol that includes performing dual confirmatory tests in the event of another "inconclusive" BSE screening test.

snip...

The animal was selected for testing because, as a non-ambulatory animal, it was considered to be at higher risk for BSE. An initial screening test on the animal in November 2004 was inconclusive, triggering USDA to conduct the internationally accepted confirmatory IHC tests. Those test results were negative. Earlier this month, USDA's Office of the Inspector General recommended further testing of the seven-month-old sample using another internationally recognized confirmatory test, the Western blot. Unlike the IHC, the Western blot was reactive, prompting USDA to send samples from the animal to the Weybridge laboratory for further analysis.

The investigation identified one feed which contained an animal protein source that could not be identified. The investigation also found one feed mill that supplied feed to the farm that had used ruminant MBM in feed formulations for non-ruminant species after the BSE/Ruminant Feed rule went into effect, which is permitted under the rule, and that several feed mills had used ruminant MBM in feeds prior to the feed ban. Although the investigation did not identify a specific feed source as the likely cause of this animal’s infection, it is probable that the most likely route of exposure for this animal was consumption of an animal feed containing mammalian protein prior to the implementation of the BSE/Ruminant Feed rule in 1997.

http://www.fda.gov/cvm/texasfeedrpt.htm

Texas BSE InvestigationFinal Epidemiology ReportAugust 2005

snip...

ProgenyThe owner did keep some replacement heifers and, although he was relatively sure that hehad not kept any offspring from the yellow cow because of her excitable demeanor, DNAanalysis of the herd revealed several animals in the herd that may have been older offspringof the index cow. While the owner sold 12 calves at the sale with the index cow on11/11/04, her last calf was not in that group. According to the owner, the index cow’s lastcalf was born either in Fall 2003 or Spring 2004, weaned early, and sold through thelivestock market some time between February and October 2004. The calf prior to thatwould have been born either in Fall 2002 or Spring 2003 and was sold at the livestockmarket sometime between January and December 2003.Birth CohortThe owner of Farm A kept very few herd records; this made finding documentation on thiscow’s birth cohort difficult. The birth cohort, by definition, included all cattle born on thepositive animal’s birth premises within 1 year, before or after, the positive animal’s date ofbirth. The index cow was approximately 12 years of age in November 2004, but there wasno exact birth date in the herd records. A potential age range of 11 to 13 years was used tosufficiently cover the animal’s most likely age. Using this range, all cattle born on theindex premises between 1990 and 1995 were considered part of the birth cohort.

snip...

Trace Herd 1The owner of Trace Herd 1 was identified as having received one of the adult COI from theindex herd. Trace Herd 1 contained 909 head of cattle in multiple pastures and was placedunder hold order on 7/21/05. Upon completion of herd inventory, the animal of interestwas not found within the herd. A GDB search of all recorded herd tests conducted onTrace Herd 1 and all market sales by the owner failed to locate the identification tag of theanimal of interest and she was subsequently classified as untraceable. The hold order onTrace Herd 1 was released on 8/8/05.Trace Herd 2Trace Herd 2 was identified as having received one of the adult COI from the index herd.Trace Herd 2 contained 19 head of cattle on one pasture and was placed under hold orderon 7/25/05. The owner of Trace Herd 2 identified the animal of interest by her eartag whilehe was feeding his cattle out of a bucket and individually penned her for inspection by fieldpersonnel. While the cow was identified as one of the animals that had left the index farm,her age by dentition was estimated to be only 5 years old, which was too young to haveplaced her as part of the birth or feed cohort of the index animal. She was classified asfound alive but determined not to be one of the COI; the hold order on Trace Herd 2 wasreleased on 7/26/05.11Trace Herd 3The owner of Trace Herd 3 was identified as possibly having received an animal ofinterest. The herd was placed under hold order on 7/27/05. The herd inventory wasconducted on 7/28/05. The animal of interest was not present within the herd, and the holdorder was released on 7/28/05. The person who thought he sold the animal to the owner ofTrace Herd 3 had no records and could not remember who else he might have sold the cowto. Additionally, a search of GDB for all cattle sold through the markets by that individualdid not result in a match to the animal of interest. The animal of interest traced to this herdwas classified as untraceable because all leads were exhausted.Trace Herd 4The owner of Trace Herd 4 was identified as having received one of the COI through anorder buyer. Trace Herd 4 was placed under hold order on 7/29/05. A complete herdinventory was conducted on 8/22/05 and 8/23/05. There were 233 head of cattle that wereexamined individually by both State and Federal personnel for all man-made identificationand brands. The animal of interest was not present within the herd. Several animals werereported to have died in the herd sometime after they arrived on the premises in April 2005.A final search of GDB records yielded no further results on the eartag of interest at eithersubsequent market sale or slaughter. With all leads having been exhausted, this animal ofinterest has been classified as untraceable. The hold order on Trace Herd 4 was released on8/23/05.Trace Herd 5The owner of Trace Herd 5 was identified as having received two COI and was placedunder hold order on 8/1/05. Trace Herd 5 is made up of 67 head of cattle in multiplepastures. During the course of the herd inventory, the owner located records that indicatedthat one of the COI, a known birth cohort, had been sold to Trace Herd 8 where she wassubsequently found alive. Upon completion of the herd inventory, the other animal ofinterest was not found within the herd. A GDB search of all recorded herd tests conductedon Trace Herd 5 and all market sales by the owner failed to locate the identification tag ofthe animal of interest and she was subsequently classified as untraceable due to all leadshaving been exhausted. The hold order on Trace Herd 5 was released on 8/8/05.Trace Herd 6The owner of Trace Herd 6 was identified as possibly having received an animal of interestand was placed under hold order on 8/1/05. This herd is made up of 58 head of cattle ontwo pastures. A herd inventory was conducted and the animal of interest was not presentwithin the herd. The owner of Trace Herd 6 had very limited records and was unable toprovide further information on where the cow might have gone after he purchased her fromthe livestock market. A search of GDB for all cattle sold through the markets by thatindividual did not result in a match to the animal of interest. Additionally, many of theanimals presented for sale by the owner of the herd had been re-tagged at the marketeffectually losing the traceability of the history of that animal prior to re-tagging. Theanimal of interest traced to this herd was classified as untraceable due to all leads havingbeen exhausted. The hold order on Trace Herd 6 was released on 8/3/05.12Trace Herd 7The owner of Trace Herd 7 was identified as having received an animal of interest and wasplaced under hold order on 8/1/05. Trace Herd 7 contains 487 head of cattle on multiplepastures in multiple parts of the State, including a unit kept on an island. The islandlocation is a particularly rough place to keep cattle and the owner claimed to have lost 22head on the island in 2004 due to liver flukes. Upon completion of the herd inventory, theanimal of interest was not found present within Trace Herd 7. A GDB search of allrecorded herd tests conducted on Trace Herd 7 and all market sales by the owner failed tolocate the identification tag of the animal of interest. The cow was subsequently classifiedas untraceable. It is quite possible though that she may have died within the herd,especially if she belonged to the island unit. The hold order on Trace Herd 7 was releasedon 8/8/05.Trace Herd 8Trace Herd 8 received an animal of interest, which happened to be a known birth cohort ofthe index cow, from Trace Herd 5. Trace Herd 8 consists of 146 head of cattle that wereplaced under hold order on 8/4/05. A herd inventory was conducted, the birth cohort wasfound alive in the herd, and she was purchased and euthanized. The hold order on TraceHerd 8 was released on 8/4/05. The cow was sampled on 8/5/05 and BSE tested by ELISAat NVSL. Results were negative (as reported on 8/6/05); carcass disposal was completedby alkaline digestion.

“We received a positive result on a Western blot confirmatory test conducted at the USDA laboratories in Ames, Iowa, on samples from an animal that had tested “inconclusive” on a rapid screening test performed on Friday, March 10.

“The samples were taken from a non-ambulatory animal on a farm in Alabama. A local private veterinarian euthanized and sampled the animal and sent the samples for further testing, which was conducted at one of our contract diagnostic laboratories at the University of Georgia. The animal was buried on the farm and it did not enter the animal or human food chains.

Summary:Despite a thorough investigation of two farms that were known to contain the index cow,and 35 other farms that might have supplied the index cow to the farms where the indexcase was known to have resided, the investigators were unable to locate the herd oforigin. The index case did not have unique or permanent identification, plus, the size andcolor of the cow being traced is very common in the Southern United States. Due to theunremarkable appearance of solid red cows, it is not easy for owners to rememberindividual animals. In the Southern United States, it is common business practice to buybreeding age cows and keep them for several years while they produce calves. Mostcalves produced are sold the year they are born, whereas breeding cows are sold whenthere is a lapse in breeding, which can occur multiple times in cows’ lives. For all ofthese reasons, USDA was unable to locate the herd of origin.

AFTER this, it was just to much risk for USDA/APHIS/FSIS et al to do anymore extensive TSE testing of any sort in the USA bovine. so they reduced BSE testing drastically ;

USDA ANNOUNCES NEW BSE SURVEILLANCE PROGRAM

WASHINGTON, July 20, 2006-Agriculture Secretary Mike Johanns announced today that the U.S. Department of Agriculture will soon begin transitioning to an ongoing Bovine Spongiform Encephalopathy (BSE) surveillance program that corresponds to the extremely low prevalence of the disease in the U.S.

"It's time that our surveillance efforts reflect what we now know is a very, very low level of BSE in the United States," said Johanns. "This ongoing surveillance program will maintain our ability to detect BSE, provide assurance that our interlocking safeguards are successfully preventing BSE, while continuing to exceed science-based international guidelines."

The ongoing BSE surveillance program will sample approximately 40,000 animals each year. Under the program, USDA will continue to collect samples from a variety of sites and from the cattle populations where the disease is most likely to be detected, similar to the enhanced surveillance program procedures.

Technical Abstract: Transmissible spongiform encephalopathy (TSE) agents induce fatal neurodegenerative diseases in humans and in some other mammalian species. Human TSEs include Creutzfeldt¿Jakob disease (CJD), Gerstmann-Sträussler-Scheinker (GSS) syndrome, Kuru and Fatal Familial Insomnia (FFI). In animals, several distinct TSE diseases are recognized: scrapie in sheep and goats, transmissible mink encephalopathy (TME) in mink, chronic wasting disease (CWD) in cervids, and bovine spongiform encephalopathy (BSE) in cattle. BSE was first detected in 1986 in the United Kingdom and is the most likely cause of variant CJD in humans. BSE in cattle is a neurological disease with a characteristic molecular pattern of the protease-resistant prion protein, PrP**res. This BSE 'signature' has also been identified in BSE-induced TSEs of both domestic cats and exotic ruminant species. Since 2004, some cases of prion diseases in cattle have been described which show unusual or atypical features as assessed by the molecular characterization of PrP**res and/or histopathology, when compared to the unique features of previously described BSE. These atypical BSE cases have been characterized by Western blot and have been referred to as H- (i.e., high molecular weight) or L-type (i.e., low molecular weight type). These atypical BSE cases have been found mainly in cattle older than 8 years. In the U.S., three cases of BSE have been diagnosed so far. Case 1 represented a typical BSE isolate, identified in an animal imported from Canada. Cases 2 and 3 were identified in animals raised in the U.S. and revealed an unusual molecular PrP**res pattern, consistent with atypical BSE cases described as H-type in Europe. It should be noted that the Western Blot method applied for BSE confirmatory tests in the U.S. has been able to detect both H-type and L-type BSE cases when using known positive European samples.

Technical Abstract: Bovine Spongiform Encephalopathy (BSE) surveillance has been ongoing in the USA since the early 1990¿s and initial testing was done at the USDA, National Veterinary Services Laboratories (NVSL) utilizing routine histopathology exclusively. In 1995, the immunohistochemistry (IHC) test was incorporated into surveillance testing in addition to routine histopathology. By 1999 virtually all BSE screening was performed by IHC and by 2001 the NVSL had switched to an automated IHC procedure. In 2002 and 2003 the NVSL tested about 20,000 high risk animals each year by IHC. In December, 2003 an animal was identified by IHC as positive for BSE (Case 1); this animal was determined to be imported from Canada. After this animal was identified, in June 2004 the USDA began its enhanced surveillance program as a shared effort between selected state veterinary diagnostic laboratories and NVSL, as part of the National Animal Health Laboratory Network. The plan called for testing as many targeted high risk animals as possible in a 12-18 month period. From June 1, 2004 through March 21, 2006, over 650,000 animals have been tested (Bio-Rad ELISA). Of those tested, two animals (Cases 2 and 3) have been identified as positive for BSE. While all three cases were strongly positive by Bio-Rad ELISA, Cases 2 and 3 have common features which are distinct from Case 1. Definitive spongiform changes in the obex, strong immunohistochemical reactions, and Western blot patterns similar to European BSE cases were observed in Case 1. In contrast, Cases 2 and 3 did not contain definitive histological lesions of BSE and the IHC staining was less intense than Case 1. In addition, Cases 2 (approximately 12 years) and Case 3 (approximately ten years) were older animals while Case 1 was 6.5 years old. Western blot analysis, PrP**Sc from Case 1 showed molecular features similar to typical BSE isolates, whereas PrP**Sc from Cases 2 and 3 revealed an unusual molecular PrP**Sc pattern: molecular mass of the unglycosylated and monoglycosylated isoform was higher than that of typical BSE isolates. Case 1 contained more PrP**Sc per brain tissue mg equivalent compared with Cases 2 and 3 using antibody 6H4. In Western Blot analysis, Case 2 and Case 3 were strongly positive with antibody P4, while Case 1 was negative or weakly positive with P4.

Bovine Amyloid Spongiform Encephalopathy (BASE) is an atypical BSE straindiscovered recently in Italy, and similar or different atypical BSE caseswere also reported in other countries. The infectivity and phenotypes ofthese atypical BSE strains in humans are unknown. In collaboration withPierluigi Gambetti, as well as Maria Caramelli and her co-workers, we haveinoculated transgenic mice expressing human prion protein with brainhomogenates from BASE or BSE infected cattle. Our data shows that about halfof the BASE-inoculated mice became infected with an average incubation timeof about 19 months; in contrast, none of the BSE-inoculated mice appear tobe infected after more than 2 years. ***These results indicate that BASE istransmissible to humans and suggest that BASE is more virulent thanclassical BSE in humans.

There is a growing number of human CJD cases, and they were presented lastweek in San Francisco by Luigi Gambatti(?) from his CJD surveillancecollection.

He estimates that it may be up to 14 or 15 persons which display selectivelySPRPSC and practically no detected RPRPSC proteins.

http://www.fda.gov/ohrms/dockets/ac/06/transcripts/1006-4240t1.htm

http://www.fda.gov/ohrms/dockets/ac/06/transcripts/2006-4240t1.pdf

JOURNAL OF NEUROLOGY

MARCH 26, 2003

RE-Monitoring the occurrence of emerging forms of Creutzfeldt-Jakob

disease in the United States

Email Terry S. Singeltary:

flounder@wt.net

I lost my mother to hvCJD (Heidenhain Variant CJD). I would like to

comment on the CDC's attempts to monitor the occurrence of emerging

forms of CJD. Asante, Collinge et al [1] have reported that BSE

transmission to the 129-methionine genotype can lead to an alternate

phenotype that is indistinguishable from type 2 PrPSc, the commonest

sporadic CJD. However, CJD and all human TSEs are not reportable

nationally. CJD and all human TSEs must be made reportable in every

state and internationally. I hope that the CDC does not continue to

expect us to still believe that the 85%+ of all CJD cases which are

sporadic are all spontaneous, without route/source. We have many TSEs in

the USA in both animal and man. CWD in deer/elk is spreading rapidly and

CWD does transmit to mink, ferret, cattle, and squirrel monkey by

intracerebral inoculation. With the known incubation periods in other

TSEs, oral transmission studies of CWD may take much longer. Every

victim/family of CJD/TSEs should be asked about route and source of this

agent. To prolong this will only spread the agent and needlessly expose

others. In light of the findings of Asante and Collinge et al, there

should be drastic measures to safeguard the medical and surgical arena

from sporadic CJDs and all human TSEs. I only ponder how many sporadic

CJDs in the USA are type 2 PrPSc?

http://www.neurology.org/cgi/eletters/60/2/176#535

Diagnosis and Reporting of Creutzfeldt-Jakob Disease

Singeltary, Sr et al. JAMA.2001; 285: 733-734.

http://jama.ama-assn.org/

BRITISH MEDICAL JOURNAL

BMJ

http://www.bmj.com/cgi/eletters/319/7220/1312/b#EL2

BMJ

http://www.bmj.com/cgi/eletters/320/7226/8/b#EL1

THE rest is history, GWs and the OIE BSE MRR policy that will spread these different strains of TSE around the globe,all for a buck, cattle futures and commodities rule, to hell with human health. OF which due to the long incubation period, ramifications of this blunder will not be felt for a decade or more later down the road. ...TSS